Bill & Melinda Gates Initiatives on Partnering for Global
Regulatory Pathways Efficiency Vincent Ahonkhai MD, FAAP October 4,
2012 CPTR 2012 Workshop
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Every person deserves the chance to live a healthy, productive
life.
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All lives have equal value Our Belief
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How We Make a Difference Focus We focus on traditionally
neglected areas that have the greatest potential for impact.
Amplify We amplify the effectiveness of proven tools through
delivery and distribution. Innovate Where tools do not exist, we
invest in innovation and research. Target We target a limited
number of long-term priorities and solutions. Complement We strive
to complement, not replace, the roles of other players.
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2011 Bill & Melinda Gates Foundation | Pre-registration
activities Registration Post-marketing activities 5 High level
product development pathway Selected critical regulatory activities
Reg. by SRA or local NRA WHO prequalification Clinical trial
authorization GMP compliance NRA & sponsor interactions /
guidance Dossier prep / filing(s) Reg. strategy / pathway selection
Safety surveillance / pharmacovigilance Licensure commitment
studies (phase 4) Product quality monitoring / anti- counterfeiting
Target NRA registration LMIC NRAs need more technical expertise to
accelerate these activities We define the regulatory landscape
through three categories of activity
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Our focus is to save lives by expanding and providing speedier
access to global health products 2011 Bill & Melinda Gates
Foundation | 6 Within foundation, provide regulatory service across
the Global Health spectrum Prioritize external customer support
according to global regional national model Ensure products
efficiently and effectively follow the appropriate regulatory
pathway with internal GH support but with partners and/or grantees
in the lead Currently, PDPs and other partners regulatory capacity
and abilities vary widely Develop and license new, low-cost
products Prequalify these products Register products in countries
of delivery Aid in the development, approval, and delivery of
vaccines, drugs and other health technologies which includes
decreasing the time required to get product to the populations that
need Driven by currently lengthy approval times impacted the
delivery of priority products (i.e., licensure, WHO
prequalificationn, country registration) Our mission We use two
principles as our guide......for performing key activities
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Pre-registration: Global health technology coalition (GHTC)
2011 Bill & Melinda Gates Foundation | 7 A group of more than
30 non-profit organizations working together to educate US
policymakers about the need for US government policies to advance
the development of new global health products GHTC members strongly
believe that an expanded role for the FDA in global health can
contribute to accelerated availability of products for NTDs and
other diseases of poverty
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Pre-registration: Building resources to support clinical trial
authorization 2011 Bill & Melinda Gates Foundation | 8
Objective to build collective knowledge amongst researchers and
reviewers......by connecting them through the Global Health Trials
website Website developed by a collaboration between many research
organizations Focus is on connecting those working on clinical
trials in resource limited settings Houses reference and training
materials for researchers and reviewers Encourages information
sharing between researchers Open access and free
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Pre-registration: History of the African Vaccine Regulatory
Forum (AVAREF) 2011 Bill & Melinda Gates Foundation | 9 Jan.
'05: Network approach to reg.of clinical trials proposed at NRA
workshop organized by WHO 2005/2006: Dev. of model reg. procedures
for countries to adapt/ adopt 2005200620072008......2012 2006:
Joint reviews of CTAs, joint GCP inspection of phase II trial of
Men. A. vaccine using model proc. Sept. '06: Birth of AVAREF
(Accra), managed by HQ/AFRO Recognition of the strength of
networking by regulators led to the creation of AVAREF in September
'06 2007-current: Annual meetings Key activities: Joint Review of
RTS,S CTA, GCP inspections Dev. & adoption of ACCTD PACTA
Project Est. African Registry PACTR Currently underway:
Formalization and expansion of network Secretariat in WHO/AFRO
Newsletter & Virtual community Potential to expand scope to
incl. medicines
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Botswana Burkina Faso Cameroon Central Africa Republic Ethiopia
Kenya Gabon Gambia Ghana Malawi Mali Mozambique Nigeria Rwanda
Senegal Sierra Leone South Africa Tanzania Uganda Zambia Zimbabwe
Pre-registration: AVAREF member countries
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Kenya 2011 Bill & Melinda Gates Foundation | 11 SRA (e.g.,
FDA, EMA) WHO PQ NRAs (e.g., East Africa) SRA / LMIC NRA Regional
NRA WHO PQ Registration: Current problems and potential solutions
LMIC 1 NRA (e.g., India, China) WHO PQ NRAs Cause of Registration
DelaysEfforts Underway to Reduce Delays Sequential review
processParallel reviews Slow WHO PQ approvalsStrengthen/fund WHO PQ
capacity; increase use of Article 58 2 PQ delayed for LMIC NRA
productsTechnical assistance/funds to LMIC NRAs (India/China)
Numerous NRA approvals required (countries statutory mandate)
Regional harmonization (e.g., 1 approval covers 5 countries in East
Africa) 1 2 3 4 1 4 3 2 Product Registration Timeline Registration
& Product Delivery 1. LMIC (low- and middle-income country)
NRAs are those emerging economies that are now playing or will play
a major role in low-cost vaccine manufacturing. 2. Article-58 is a
new regulatory pathway set up by the EMA and WHO to provide an EMA
opinion and simultaneous WHO prequalification for products intended
for use in non-European markets (i.e., low-income countries) Today
Future OR Article 58 2
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2011 Bill & Melinda Gates Foundation | Initial focus
Regional registration platforms Common requirements / guidelines /
format Joint assessments / inspections Streamlined decision
processes Work sharing / pooling of resources Accelerated
registration......initially for licensed drugs
(generics)...extending to other product categories (NCEs, vaccines,
diagnostics/devices) extending to other regulatory functions over
time (clinical trials, safety surveillance, etc.) 12 Registration:
African Medicines Regulatory Harmonization Collaboration for
increased access to safe, effective, quality products AMRH
Complements existing regional harmonization efforts (ASEAN, PANDRH,
etc.) Is a joint effort formalized in 2009 and launched in East
Africa in early 2012 Includes African countries (regulatory
authorities) and regional groups (RECs); WHO; NEPAD; Gates
Foundation; DFID, World Bank; many others Aims to improve the
fragmented system of product registration in Africa by focusing on
regions within the continent (e.g., East Africa, West Africa)
Proposes to harmonize and streamline the registration process for
regulators and manufacturers, leading to increased and timely
access to products Creates a platform on which to build African
regulatory capacity by region Pilot in East Africa (EAC) Launched
March 2012
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2011 Bill & Melinda Gates Foundation | 13 1. The East
African Community (EAC) membership consists of Kenya, Tanzania,
Uganda, Rwanda, and Burundi 4. AMRH is the African Medicines
Regulatory Harmonization initiative that is backed by the
foundation, DFID, the AU, WHO, World Bank, and others.
Registration: Pilot approach to harmonized registration Joint
review/assessment led to faster registration in East Africa
Community (EAC 1 ) AMRH 2 : Regionalized Registration (multiple
countries) Products Abacavir (ARV) Amikacin (second-line TB drug)
One common product dossier submitted Single joint assessment by
team from WHO and NRA Officials from the region
(Kenya/Tanz./Uganda) AMRH would speed the introduction of priority
drugs and vaccines in all participating African countries
ActivityMonths Assessment and PQ decision completed:< 9
Independent country licensure post-PQ: Additional work looks at
country risk/benefit (e.g., storage, admin, genetic factors, etc.)
2-6 Total time to PQ/approval in pilot countries:
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2011 Bill & Melinda Gates Foundation | Registration:
Foundation and WHO partnership is focused on improving
prequalification (PQ) 14 Implement recommended reform Uniform
policy across all PQ programs vaccines, medicines,
devices/diagnostics Increased efficiency (reduced time; more
parallel processing) Concrete steps toward self-sustainability
Address deficiencies in the diagnostics PQ program Develop
international quality standards Improve program management and
leadership support Increase efficiency to reduce
delays/complexity
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Post-marketing: Safety surveillance working group Developing
solutions for post-market monitoring in low resource environments
2011 Bill & Melinda Gates Foundation | 15 Industry Academic
experts Regulators/ WHO Other GH organizations Foundation sponsored
forum seeking to identify practical, scalable strategies for
improving safety surveillance of drugs and vaccines in LMICs 1
Number of GH products entering LMICs expected to increase Historic
focus on market entry of products vs. pharmacovigilance Resultant
lack of funding mechanisms for safety surveillance 1. LMIC = Low
and middle-income countries This newly formed group will be
publishing a white paper on safety surveillance strategy in early
2013 Donor organizations
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The importance of successful partnering Case study: Meningitis
A vaccine development MVP Core Team Tetanus toxoid Process
Development Manufacturing Men A Polysaccharide Conjugation method
Target price US$
Pharmacovigilance studies conducted before introduction of
vaccine to the broader population Solicited advice from WHO Global
Advisory Committee on Vaccine Safety Pharmacovigilance studies done
in Burkina Faso, Mali and Niger (1.2 million vaccinated in Sept
2010) Single dose in 1 to 29 year olds in catch up vaccination
campaigns to rapidly induce herd immunity Burkina Faso, Mali and
Niger introductions (Dec 2010) were well received with very high
coverage (>90 percent) Pharmacovigilance studies Vaccine
introduction
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YearCasesDeathsCFR No. epid. district % Men A % Pneumo
20053,62674620.6111.649.5 200619,1341,6748.73484.69.4
200726,8781,9237.24391.17.1 200810,4011,06710.32079.219.3
20094,72362913.3330.166.7 20106,73294914.11224.947.5 Introduction
of MenAfriVac in December 2010 2011 (wk 16) 2,27438917.021.073.5
Table: Meningitis cases, deaths and case fatality ratio with
percent distribution of group A meningococcal and pneumococcal
isolates: burkina faso, 2005-2011 Data shows dramatic decrease in
incidence and fatality
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Early success expected to translate into long-term benefits
Dramatic reduction in reported meningitis cases including epidemic
districts in 2011 Virtual disappearance of meningitis due to Group
A Neisseria meningitidis As a result a higher fraction of
pneumococcal CSF isolates Stable fraction of non Group A
meningococcal isolates in 2011
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2011 Bill & Melinda Gates Foundation | 21 Questions?
